Energy metabolism in neurodevelopment and medulloblastoma

Translational Pediatrics
Katherine Tech, Timothy R Gershon

Abstract

New, less toxic therapies are needed for medulloblastoma, the most common malignant brain tumor in children. Like many cancers, medulloblastomas demonstrate metabolic patterns that are markedly different from the surrounding non-neoplastic tissue and are highly organized to support tumor growth. Key aspects of medulloblastoma metabolism, including increased lipogenesis and aerobic glycolysis are derived from the metabolic programs of neural progenitors. During neural development, Sonic Hedgehog (Shh) signaling induces lipogenesis and aerobic glycolysis in proliferating progenitors to support rapid growth. Shh-regulated transcription induces specific genes, including hexokinase 2 (Hk2) and fatty acid synthase (FASN) that mediate these metabolic patterns. Medulloblastomas co-opt these developmentally-regulated patterns of metabolic gene expression for sustained tumor growth. Additionally, medulloblastomas limit protein translation through activation of eukaryotic elongation factor 2 kinase (eEF2K), to restrict energy expenditure. The activation of eEF2K reduces the need to generate ATP, enabling reduced dependence on oxidative phosphorylation and increased metabolism of glucose through aerobic glycolysis. Lipogenesis, aerobic gly...Continue Reading

Citations

Oct 27, 2018·International Journal of Molecular Sciences·Honglai ZhangJean-François Rual

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